The coagulation system Flashcards
What is Virchow’s Triad?
Stasis of blood flow
Hyper coagulability - components of blood
Vascular Injury - blood vessels
Describe stasis
Immobility - post op state, debility, coma --> ICU or medical ward - Economy class syndrome Pressure - Catheter (Central line blockage) or tumour obstruction Increased viscosity - Polycythemia - Dehydration - EPO
Blood hyper coagulability (mainly venous thrombosis)
Increased procoagulants (factor VIII) Decrease in inhibitors
what is a VT (venous thromboembolism)
DVT or PE = 2 potential presentations of the same disease
PE slightly less common than a DVT
Signs and symptoms of 1.DVT and 2.PE
DVT: - Leg swelling - Leg pain - Oedema PE - Shortness of breath - Chest pain - Tachycardia -Tachypnoea All these symptoms are nonspecific and common making it hard to diagnose, use diagnostic algorithms (e.g. wells score) to be more accurate
What are D-dimers?
Breakdown products of fibrin
Positive in the 83-98% of DVT and PE (depending on method)
Also positive in patients without VTE - inflammation and surgery
Test not very accurate: high false negative and low true positive
Should be interpreted with a clinical score
When do you use the D-dimer testing when you’re suspicious that a patient has a DVT off the wells score
IF clinical score shows low probability of DVT
test for D-dimers
if negative then discharge
If positive send for scan
What is the diagnostic scan for DVT?
US!! doppler
3/4 of symptomatic DVT are proximal (popliteal and above) if untreated half will embolise to the lung
IF patient turns up with DVT what are some casual factors you should check for?
CANCER!!
e.g. if 60 yr old male has recent unexplained weight loss and iron deficiency then do colonoscopy
Classic symptom triad of PE
+ classic sings
Symptoms:
pleuritic pain
Shortness of breath
Haemoptysis
Signs:
Tachycardia
Tachypnoea
Hypoxia
Prognosis of a massive PE
Sudden death 15%
Mortality >50%
Hypotension
severe right heart pain due to back pressure from pulmonary arteries
What is thromboplilia
Tendency to develop thrombosis can be acquired or inherited or both Term usually applied to hereditary manifested as VTE multi hit theory
causes of VTE
30-40% spontaneous - about 50% of these have a hereditary factor which increases risk: thrombophilia Remainder provoked - surgery or trauma - immobility - hospitalisation - malignancy - HRT/OCP/pregnancy other e.g. myeoloproliferative diseases
Is travel immobility a huge risk factor for VTE?
No
OCP and obesity far worse
Inherited thrombophilia
Abnormal inhibitor function
- Resistance to activated protein C (Factor V Leiden)
Deficiency of inhibitors
- antithrombin, protein C or S deficiency
- RARE, also deficiency of these factors doesn’t affect the APTT (heparin, dibigitran and lupus anticoagulant do)
Factor V leiden
point mutation of arginine at position 506 in factor V molecule with glutamine
The most common hereditary cause of thrombophilia
4% of northern europeans
Activated protein C unable to cleave factor V leiden
factor Xa activation continues
Va levels ~20% higher
Heparin as a treatment for anticoagulation
An inhibitor through increased antithrombin effect APTT 1+1 is prolonged, TCT markedly prolonged
reversed in the lab and clinically with protamine
Required antithrombin inactivation of Xa and IIa (thrombin)
LMW heparin
Similar to IV heparin - smaller glycosaminoglycan chains Accelerates the antithrombin inhibition of Xa rather than inhibiting thrombin, so has less effect on APTT, so can't use APTT to monitor drug effects Subcutaneous with better bioavilablity Packaged vials Enoxiparin weight based dose
Treatment plan for anticoagulation
LMW heparin
Warfarin at same time min 5 days overlap
Alternatively a novel oral agent
Inhibits coagulation, allows own fibrinolytic mechanisms to operate unhindered by further clotting (doesn’t break clots down, just prevents more from forming)
Warfarin negatives
Needs monitoring
Risk of interactions with many drugs - antibiotics, anticonvulsants, amiodarone, diltiazem, citalopram
High INR increases bleeding risk further
takes time for reduced available via K to reduce activation of active clotting factors… 5-7 days to a therapeutic level, prothrombin half life = 2 days
monitored using the prothrombin ratio
INR 2-3 is the therapeutic range
How to reverse the effects of warfarin
Vit K IV - 12 to 24 hours for the clotting factors to be made
If immediate reversal required
- prothrombinex (contains clotting factors II, IX and X)
Direct acting oral anticoagulants (DOAC’s)
Oral direct inhibitors of activated clotting factors
Half life 9-14 hours
Rivaroxaban (Xa) and dibigitran (thrombin or IIa) are both the same as warfarin for the treatment of VTE
probably superior to warfarin for anticoagulation in AF - better stroke prevention with similar rates of bleeding
DOAC’s
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+ no monitoring needed, fixed dose
+ less intracranial haemorrhage (vs warfarin)
- people with renal failure (esp on dibigitran) can accumulate very high levels
The difference between rivaroxaban and dibigitran
rivaroxaban acts on factor Xa so has much more subtle effects than dibigitran which acts on thrombin
Dibigitran TCT extremely sensitive
- APTT prolonged at therapeutic levels (1+1 prolonged)
- PR prolonged if very high
Rivaroxaban: PR prolonged to some extent, APTT less so
Specific assay for both
DOAC reversal
dibigitran antidote = idarucizumab
- antibody that binds to dibigitran
- injected in two vials
- immediately reverses almost all dibigitran effect
- may rebound at 24-48 hours if levels very high or renal impairment
- side effects rare
Morbidity of VTE patients
unto 30% of DVT patients develop post thrombotic syndrome
- Pain / swelling / oedema, redness, venous eczema, ulceration
- Graduated compression stockings help manage symptoms
2% of PE patients develop chronic thromboembolic pulmonary hypertension
- SOBOE, dizziness, fatigue
